crossing96/oncoscreening huggingface dataset:
Fibroblast growth factor receptor 3 alterations and response to immune checkpoint inhibition in metastatic urothelial cancer: a real world experience.	BACKGROUND: FGFR3-altered urothelial cancer (UC) correlates with a non-T cell-inflamed phenotype and has therefore been postulated to be less responsive to immune checkpoint blockade (ICB). Preclinical work suggests FGFR3 signalling may suppress pathways such as interferon signalling that alter immune microenvironment composition. However, correlative studies examining clinical trials have been conflicting as to whether FGFR altered tumours have equivalent response and survival to ICB in patients with metastatic UC. These findings have yet to be validated in real world data, therefore we evaluated clinical outcomes of patients with FGFR3-altered metastatic UC treated with ICB and investigate the underlying immunogenomic mechanisms of response and resistance. METHODS: 103 patients with metastatic UC treated with ICB at a single academic medical center from 2014 to 2018 were identified. Clinical annotation for demographics and cancer outcomes, as well as somatic DNA and RNA sequencing, were performed. Objective response rate to ICB, progression-free survival, and overall survival was compared between patients with FGFR3-alterations and those without. RNA expression, including molecular subtyping and T cell receptor clonality, was also compared between FGFR3-altered and non-altered patients. RESULTS: Our findings from this dataset confirm that FGFR3-altered (n = 17) and wild type (n = 86) bladder cancers are equally responsive to ICB (12 vs 19%, p = 0.73). Moreover, we demonstrate that despite being less inflamed, FGFR3-altered tumours have equivalent T cell receptor (TCR) diversity and that the balance of a CD8 T cell gene expression signature to immune suppressive features is an important determinant of ICB response. CONCLUSIONS: Our work in a real world dataset validates prior observations from clinical trials but also extends this prior work to demonstrate that FGFR3-altered and wild type tumours have equivalent TCR diversity and that the balance of effector T cell to immune suppression signals are an important determinant of ICB response.	bladder
Circular RNA circSETD3 hampers cell growth, migration, and stem cell properties in bladder cancer through sponging miR-641 to upregulate PTEN.	Bladder cancer (BLCA) is a common malignant urothelial cancer in the world. Although circular RNAs (circRNAs) involve in regulating BLCA progression, the role of a novel circular RNA circSETD3 in regulating BLCA pathogenesis has not been studied. The expression of circSETD3, miR-641, PTEN mRNA in BLCA tissues and cell lines were measured using RT-qPCR. The gain-of-function experiments were performed in vitro and in vivo to detect the effects of circSETD3 on cell proliferation, migration, EMT, and stemness maintenance. Besides, rescue experiments were performed to demonstrate the regulatory mechanism of circSETD3/miR-641/PTEN in BLCA cell malignant phenotypes in vitro. CircSETD3 was remarkably downregulated in the cancerous clinical tissues and cell lines, in contrast with their normal counterparts, and circSETD3 tended to be deficient in BLCA patients with larger tumor size, advanced clinical stages, positive lymph metastasis and worse prognosis. In addition, circular isoforms of circSETD3 were more resistant to RNase R+ and actinomycetes D treatment compared to their linear isoforms, and circSETD3 mainly distributed in the cytoplasm of the BLCA cells. Further gain-of-function experiments showed that circSETD3 acted as a tumor suppressor to suppress BLCA cell proliferation, migration, EMT and stemness, and the underlying mechanisms had also been elucidated. Mechanistically, circSETD3 sponged miR-641 to upregulate PTEN, resulting in the blockage of BLCA progression. Our findings indicated that circSETD3 acted as a vital tumor suppressor in BLCA via regulating the miR-641/PTEN axis.	bladder
Socio-Environmental Conditions Associated with Geospatial Clusters of Urothelial Carcinoma: A Multi-Institutional Analysis.	PURPOSE: The interaction between sources of industrial byproducts and environmental pollutants (IBP/EP) and the prevalence of urothelial carcinoma (UC) in surrounding communities has been infrequently explored. The purpose of this research is to identify microregional UC hotspots and associated industrial and environmental risk factors. MATERIALS AND METHODS: We retrospectively queried a multi-institutional database for UC patients diagnosed between 2008 and 2018. Addresses were geocoded and used to perform hotspot analysis on the census block level. Demographic and clinicopathological characteristics, census data and proximity to sources of IBP/EP were compared between patients who did vs did not reside in a hotspot. Associations were tested using multilevel logistic regression models using 95% confidence intervals. RESULTS: A total of 5,080 patients met inclusion criteria and 148 (2.9%) were identified as living in 1 of 3 UC hotspots. In univariate analyses, race, tobacco and alcohol use, household income, IBP/EP exposure and proximity to traffic, industrial discharge and airports were significantly associated with UC hotspots. Multivariable analysis demonstrated that polycyclic aromatic hydrocarbon exposure (OR: 48.09, p ≤0.001) and proximity to high-density traffic (OR: >999, p ≤0.001) increased the odds of living in a hotspot. Patients living in a hotspot were significantly less likely to be white (OR: 0.06, p ≤0.001) or tobacco users (OR: 0.39, p=0.031) on multivariate analysis. CONCLUSIONS: Spatially related clusters of UC may be associated with locoregional environmental exposures rather than tobacco exposure and may also be correlated with socioeconomic disparities. Geospatial analysis can help to identify at-risk populations, offering the opportunity to better focus preventive and diagnostic interventions.	bladder
Gas6 expression and Tyrosine kinase Axl Sky receptors: Their relation with tumor stage and grade in patients with bladder cancer.	OBJECTIVES: It has been shown that the dysregulation of tyrosine kinase Axl receptor and its ligand growth arrest-specific gene (Gas6) are associated with poor prognosis in various types of tumors but there is not enough study about their importance in bladder cancer (BC). We evaluated the relation of Gas6 gene expression and tyrosine- kinase Axl and Sky (Tyro 3) receptors with tumor stage and grade in patients with BC. MATERIAL AND METHODS: The study group consists of 55 patients whose transurethral resection of bladder (TUR-B) has been performed due to BC and the control group consists of 12 patients with normal bladder mucosa. In tissues mRNAs of Gas6, Axl, and Sky receptors were examined by quantitative (Real-Time) PCR (qPCR). Protein expression was measured by immunohistochemistry. Plasma Gas6 protein levels were compared with control group by ELISA method. RESULTS: Patients with BC were grouped as Ta low (n=17), Ta high (n=5), T1 low (n=9), T1 high (n=8) and T2 (n=16) according to their TUR-B pathologies. The qPCR analysis showed that the expression of Gas6 gene and Axl receptor is higher in the tumor-positive group and the immune-histochemical showed that the bladder samples of the tumor-positive group stained significantly positive. When the patients are grouped according to the TUR-B pathologies, a statistical significant difference was observed among groups in the qPCR analysis ratios of Gas6 gene and Axl receptor by (p < 0.05) but no significance was found for Sky receptor (p > 0.05). When Gas6 protein levels in plasma samples were compared by ELISA method, a statistical significance was determined among groups (p = 0.001). CONCLUSIONS: Our findings indicate that mRNAs of Gas6 and Axl receptor are closely related to tumor stage and grade in patients with BC. Further studies are needed for understanding the role of Gas6 and its receptors on the neoplastic transformation in terms of novel biomarkers and potential therapeutic targets.	bladder
Endothelin-1 indicates unfavorable prognosis in primary high-grade non-muscle-invasive urothelial bladder cancer.	OBJECTIVE: To conduct a prospective study of the potential prognostic role of endothelin-1 (ET-1) in a cohort of primary high-grade non-muscle-invasive urothelial bladder cancer patients, who were treated with adjuvant intravesical Bacillus Calmette-Guérin (BCG). MATERIAL AND METHODS: Patients with primary high-grade nonmuscle- invasive urothelial bladder cancer, who received postoperatively induction and maintenance BCG therapy, were prospectively included. Recurrence and progression were histologically proven. Immunohistochemical staining for ET-1 was assessed. Epidemiological, pathological and clinical parameters as well as the expression of ET-1 in tumor specimens were statistically analyzed for recurrence, progression, recurrence-free survival (RFS) and progression-free survival (PFS). RESULTS: ET-1 associates significantly with recurrence (p = 0.000), progression (p = 0.000), RFS (p = 0.000) and PFS (p = 0.000). The patient's age is also significant for recurrence (p = 0.003, OR = 1.273 95% CI: 1.086-1.492) and RFS (p = 0.013). CONCLUSIONS: ET-1 seems to deteriorate prognosis in patients suffering from primary high-grade non-muscle-invasive urothelial bladder cancer, who are treated with adjuvant BCG instillations. Furthermore, the patient's age associates with an increased likelihood for recurrence.	bladder
High-throughput sequencing identified circular RNA circUBE2K mediating RhoA associated bladder cancer phenotype via regulation of miR-516b-5p/ARHGAP5 axis.	Bladder cancer (BC) is known as a common and lethal urinary malignancy worldwide. Circular RNAs (circRNAs), an emerging non-coding RNA, participate in carcinogenesis process of several cancers including BC. In this study, high-throughput sequencing and RT-qPCR were applied to discover and validate abnormal high expression of circUBE2K in BC tissues. Fluorescence in situ hybridization (FISH) was used to detect hsa_circ_0009154 (circUBE2K) expression and subcellular localization in BC tissues. High circUBE2K predicted unfavorable prognoses in BCs, as well as correlated with clinical features. CCK8, transwell, EdU and wound healing assays demonstrated down-regulating circUBE2K decreased BC cell phenotype as proliferation, invasion, and migration, respectively. Further studies showed that circUBE2K promoted BC progression via sponging miR-516b-5p and enhancing ARHGAP5 expression through regulating RhoA activity. Dual-luciferase reporter, FISH and RNA pulldown assays were employed to verify the relationships among circUBE2K/miR-516b-5p/ARHGAP5/RhoA axis. Down-regulating miR-516b-5p or overexpressing ARHGAP5 restored RhoA activity mediated BC cell properties after silencing circUBE2K. Subcutaneous xenograft and metastasis model identified circUBE2K significantly increased BC cell metastasis and proliferation in-vivo. Taken together, we found that circUBE2K is a tumor-promoting circRNA in BC that functions as a ceRNA to regulate ARHGAP5 expression via sponging miR-516b-5p.	bladder
Vaginal Complications after Radical Cystectomy for Bladder Cancer: A Systematic Review.	OBJECTIVES: To summarize the published literature regarding pelvic organ prolapse, dehiscence or evisceration, vaginal fistula, and dyspareunia after radical cystectomy and to describe the management approaches used to treat these conditions. METHODS: Ovid MEDLINE, Ovid EMBASE, and Web of Science were systematically searched from January 1, 2001 to January 25, 2021 using a combination of search terms for bladder cancer and radical cystectomy with terms for four categories of vaginal complications (prolapse, fistula, evisceration/dehiscence, and dyspareunia). A total of 229 publications were identified, the final review included 28 publications. RESULTS: Neobladder vaginal fistula was evaluated in 17 publications, with an incidence rate of 3 - 6% at higher volume centers, often along the anterior vaginal wall at the location of the neobladder-urethral anastomosis. Sexual function was evaluated in 10 studies, 7 of which utilized validated instruments. Maintaining the anterior vaginal wall and the distal urethra appeared to be associated with improved sexual function. Pelvic organ prolapse was assessed in 5 studies, only 1 used a validated questionnaire and none included a validated objective measure of pelvic organ support. CONCLUSION: There is a need for more prospective studies, using standardized instruments and subjective outcome measures to better define the incidence of vaginal complications after radical cystectomy for bladder cancer, and to understand their impact on quality of life measures.	bladder
NECTIN4 Heterogeneity and Molecular Diversity in Bladder Cancers: Deconstructing the Activity of An Antibody-Drug Conjugate.	Nectin-4 is the target for enfortumab vedotin, a novel antibody-drug conjugate. NECTIN4 gene expression differs considerably across different molecular subtypes and is shown to be important for enfortumab vedotin efficacy.See related article by Chu et al., p. 5123.	bladder
Ceruloplasmin Levels in Cancer Tissues and Urine Are Significant Biomarkers of Pathological Features and Outcome in Bladder Cancer.	BACKGROUND/AIM: A previous report showed that immune complex-ceruloplasmin (CP) in urine is associated with carcinogenesis and malignant behavior in bladder cancer (BC). We investigated the pathological significance and prognostic roles of urine and tissue levels of CP protein in BC patients. MATERIALS AND METHODS: Urine CP levels were measured using an enzyme-linked immunosorbent assay in 97 patients. CP expression in BC tissues was evaluated by immunohistochemical analysis in 176 patient samples. RESULTS: Urine CP levels were positively associated with tumor grade and pT stage in non-muscle invasive BC (NMIBC). CP expression in BC tissues was positively associated with tumor growth and progression. Multivariate analysis demonstrated that high urine CP levels was an independent predictor of recurrence in the urinary tract in NMIBC (hazard ratio=2.87, p=0.016). CONCLUSION: CP-related markers, especially urine CP levels, are useful biomarkers of malignant potential and prognosis in NMIBC.	bladder
Epidermal Growth Factor Based Targeted Toxin for the Treatment of Bladder Cancer.	BACKGROUND/AIM: Reports on over-expression of the epidermal growth factor receptor (EGFR) in bladder cancer and its function in tumorigenesis have suggested to target this antigen. MATERIALS AND METHODS: We generated the targeted toxin EGF-PE40 consisting of the human epidermal growth factor (EGF) as the binding domain and PE40, a truncated version of Pseudomonas Exotoxin A, as the toxin domain. EGF-PE40 was tested on EGFR-expressing bladder cancer cells in view of binding via flow cytometry, and cytotoxicity via WST viability assay. Induction of apoptosis was examined by western blot. RESULTS: The targeted toxin specifically triggered cytotoxicity in the bladder cancer cells with 50% inhibitory concentration (IC(50)) values in the low nanomolar or picomolar range, and was about 1,250- to 1,500-fold more cytotoxic than the EGFR inhibitor erlotinib. Cytotoxicity of EGF-PE40 was based on the induction of apoptosis. CONCLUSION: EGF-PE40 represents a promising candidate for the future treatment of bladder cancer.	bladder
A hypoxia related long non-coding RNA signature could accurately predict survival outcomes in patients with bladder cancer.	Hypoxia plays a significant role in tumor progression. This study aimed to develop a hypoxia-related long noncoding RNA (lncRNA) signature for predicting survival outcomes of patients with bladder cancer (BC). The transcriptome and clinicopathologic data were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression analysis and Lasso regression analysis were used to screened lncRNAs. Ten lncRNAs were screened out and included into the hypoxia lncRNA signature. The risk score based on hypoxia lncRNA signature could accurately predict the survival outcomes of BC patients. Immune infiltration analysis showed that six types of immune cells had significant different infiltration. Tumor mutation burden (TMB) analysis showed that the risk scores between the wild types and the mutation types of TP53, FGFR3, and RB1 were significantly different. Gene Set Enrichment Analysis (GSEA) showed that cancer-associated pathways belonged to the high risk groups and immune-related signal pathways were enriched into the low risk group. Then, we constructed a predictive model with the risk score, age, and clinical stage, which showed a robust prognostic performance. An lncRNA-mRNA coexpression network was constructed, which contained 62 lncRNA-mRNA links among 10 lncRNAs and 40 related mRNAs. In summary, the hypoxia lncRNA signature could accurately predict prognosis, chemotherapy and immunotherapy response in patients with BC and was relevant to clinicopathologic parameters and immune cell infiltration.	bladder
BMI1 activates P-glycoprotein via transcription repression of miR-3682-3p and enhances chemoresistance of bladder cancer cell.	Chemoresistance is the most significant reason for the failure of cancer treatment following radical cystectomy. The response rate to the first-line chemotherapy of cisplatin and gemcitabine does not exceed 50%. In our previous research, elevated BMI1 (B-cell specific Moloney murine leukemia virus integration region 1) expression in bladder cancer conferred poor survival and was associated with chemoresistance. Herein, via analysis of The Cancer Genome Atlas database and validation of clinical samples, BMI1 was elevated in patients with bladder cancer resistant to cisplatin and gemcitabine, which conferred tumor relapse and progression. Consistently, BMI1 was markedly increased in the established cisplatin- and gemcitabine-resistant T24 cells (T24/DDP&GEM). Functionally, BMI1 overexpression dramatically promoted drug efflux, enhanced viability and decreased apoptosis of bladder cancer cells upon treatment with cisplatin or gemcitabine, whereas BMI1 downregulation reversed this effect. Mechanically, upon interaction with p53, BMI1 was recruited on the promoter of miR-3682-3p gene concomitant with an increase in the mono-ubiquitination of histone H2A lysine 119, leading to transcription repression of miR-3682-3p gene followed by derepression of ABCB1 (ATP binding cassette subfamily B member 1) gene. Moreover, suppression of P-glycoprotein by miR-3682-3p mimics or its inhibitor XR-9576, could significantly reverse chemoresistance of T24/DDP&GEM cells. These results provided a novel insight into a portion of the mechanism underlying BMI1-mediated chemoresistance in bladder cancer.	bladder
Approaches to Non-Muscle-Invasive Bladder Cancer.	PURPOSE OF REVIEW: Non-muscle-invasive bladder cancer (NMIBC) is a heterogenous malignancy with high recurrence and progression rates, which necessitate uniform recommendations for diagnosis and management. Herein, we review the literature, with an emphasis on guidelines and contemporary diagnostic techniques and interventions. RECENT FINDINGS: Guidelines around the world have adopted a schema which risk-stratify cases at diagnosis, to offer evidence-based treatment and surveillance recommendations. Enhanced endoscopic technologies can improve detection of NMIBC and reduce recurrence. The present Bacillus Calmette-Guerin (BCG) shortage in the USA has led to new strategies to prioritize the most high-risk cases. The entity of BCG-unresponsive high-risk NMIBC remains a challenge to manage, with multiple novel treatments under investigation; fortunately, new therapies have been approved, such as immune checkpoint inhibitors, and others are showing tremendous promise. The standardization of NMIBC management, with evolving detection techniques and therapeutics, offers great potential to improve patient outcomes and survivorship.	bladder
Association of obesity and other anthropometric characteristics with bladder cancer risk: a systematic review and meta-analysis of longitudinal cohort studies.	PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate the potential associations between anthropometric characteristics and bladder cancer risk, synthesizing longitudinal cohort studies. METHODS: Literature search across MEDLINE, EMBASE, Scopus, Google Scholar and Cochrane Central was performed up to December 31, 2019 and data abstraction was performed independently by two authors. Random-effects (DerSimonian-Laird) models were used to estimate pooled relative risks (RR) and 95% confidence intervals (95%CI); subgroup analyses were performed in geographical region, mean age, publication year, length of follow-up, sample size, method of body mass index (BMI) estimation and adjustment for smoking. RESULTS: 27 studies were included (88 593 bladder cancer cases in a total cohort of 49 647 098 subjects). Increased bladder cancer risk was noted in overweight men (pooled RR=1.12, 95%CI: 1.04-1.21) but not in overweight women. Both obese men (pooled RR=1.14, 95%CI: 1.06-1.22) and women (pooled RR=1.19, 95%CI: 1.02-1.38) showed increased risk. Interestingly, height increase per 5 cm did not seem to affect risk of bladder cancer in men (pooled RR=1.03, 95%CI: 0.99- 1.06) and women (pooled RR=1.02, 95%CI: 0.97-1.06). Larger waist circumference was associated with bladder cancer risk in men (pooled RR=1.18, 95%CI: 1.09-1.26) but not women. CONCLUSION: Bladder cancer risk seems to be related with obesity overall and central obesity in men. In contrast to other cancer types, height does not seem to affect risk, but more studies are needed to extract safe conclusions.	bladder
The relation between tissue galectin-3 level and platinum resistance in neoadjuvant bladder cancer treatment.	PURPOSE: This study aimed to reveal the relationship between the level of galectin-3 expression and the depth of response to neoadjuvant therapy in bladder tumor tissue with muscle invasion revealed by transurethral biopsy. METHODS: The percentage of galectin-3 staining in transurethral biopsy tissue with muscle invasion was determined by immunohistochemistry. The patients were divided into two groups: the down-staging (+) group consisting of patients with pathological complete response or non-invasive bladder cancer, and the down-staging (-) group consisting of patients with stage 2 and above. RESULTS: There were 11 patients in the down-staging (+) group and 12 patients in the down-staging (-) group. There was no significant difference between the two groups in terms of median age, gender, smoking, clinical stage at the time of diagnosis, distribution of carboplatin or cisplatin used as a platinum agent. Galectin-3 was positive in 2 patients (18.2%) in the group where down-staging was achieved with neoadjuvant therapy, while it was positive in 9 patients (75%) in the other group (p = 0.01). The median follow-up period of the patients was 31.6 months (95% CI 25.1-39.3). Overall survival was 43.4 months in the down-staging (+) group (95% CI 25.1-61.6) and 31.6 months in the down-staging (-) group (95% CI 12.7-50.6). Although there was a numerical difference, it did not reach statistical significance (p=0.37). CONCLUSION: The rate of down-staging after platinum-based neoadjuvant chemotherapy is significantly higher in patients with low galectin-3 staining in transurethral bladder biopsy tissue.	bladder